Disease relevance of SRGN

• Expression of PRG1 mRNA was observed in several normal breast epithelial and breast cancer cell lines and in a variety of human tissues, with highest expression in the breast, aorta, and brain [1].
• We mapped the DNase I-hypersensitive sites (DHSS) of the serglycin gene in resting and phorbol 12-myristate 13-acetate (PMA)-stimulated human erythroleukemia (HEL) and CHRF 288-11 cells, which have megakaryocytic characteristics, and HL-60 promyelocytic leukemia cells [2].
• DNase I hypersensitivity patterns of the serglycin proteoglycan gene in resting and phorbol 12-myristate 13-acetate-stimulated human erythroleukemia (HEL), CHRF 288-11, and HL-60 cells compared with neutrophils and human umbilical vein endothelial cells [2].
• Serglycin expression in CD2+ and CD14+ cells from patients with various rheumatic diseases [3].
• Cells derived from a serglycin-processing mouse mastocytoma expressed a protein highly similar to other mammalian heparanases [4].

Psychiatry related information on SRGN

• Testosterone levels, sexual interest preference by visual reaction time (Abel Assessment), penile tumescence (Monarch Penile Plethysmography, PPG), as well as strong sexual urges toward children and masturbatory frequency involving thoughts of children (polygraph), were measured every 3 months [5].

High impact information on SRGN

• Cytotoxic cell granule-mediated apoptosis: perforin delivers granzyme B-serglycin complexes into target cells without plasma membrane pore formation [6].
• Contrary to the view that PFN acts as a gateway for granzymes through the plasma membrane, monomeric PFN and, strikingly, PFN-SG complexes were shown to mediate cytosolic delivery of macromolecular GrB-SG without producing detectable plasma membrane pores [6].
• These results indicate that granule-mediated apoptosis represents a phenomenon whereby the target cell perceives granule contents as a multimeric complex consisting of SG, PFN, and granzymes, which are, respectively, the scaffold, translocator, and targeting/informational components of this modular delivery system [6].
• Recent evidence indicates that the physiological apoptosis-inducing form is a multi-component macro-complex consisting of cationic granule proteins non-covalently linked to the chondroitin-sulfate proteoglycan, serglycin [7].
• PPG arose in an early ancestor of anthropoids (catarrhines and platyrrhines), and GGTA1 itself became an unprocessed pseudogene in the late catarrhine stem lineage [8].

Chemical compound and disease context of SRGN

• This study has determined the effects of phorbol-12-myristate-13-acetate (PMA) and dimethylsulfoxide (DMSO) on mRNA levels for the serglycin proteoglycan core protein in human erythroleukemia (HEL) cells [9].
• Expression of mRNA for serglycin core protein and other platelet alpha granule proteins is increased in human erythroleukemia cells by phorbol myristate acetate [9].
• In this study, we undertook to clarify the relationship between P-glycoprotein positivity (%PPG) and doxorubicin binding ability (%DB) in human osteosarcomas in order to determine which is a more sensitive index of histologic response to chemotherapy [10].
• The addition of MC produced erythema and an increase in the amplitude of PPG tracings [11].
• Human megakaryocytic tumor cell lines CHRF-288-11 and HEL (human erythroleukemia) were incubated with antisense phosphodiester (PDE) and phosphorothioate (PS) oligodeoxynucleotides directed against the first six codons of the human serglycin proteoglycan gene [12].

Biological context of SRGN

• Cloning of the complete coding region of PRG1 revealed that it shared a high degree of amino acid sequence identity with isoforms of the enzyme 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase from several tissues and species [1].
• Identification of PRG1, a novel progestin-responsive gene with sequence homology to 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase [1].
• The granzyme B-serglycin complex from cytotoxic granules requires dynamin for endocytosis [13].
• The complete nucleotide sequence of the 16.7-kb human gene that encodes the peptide core (serglycin) of a secretory granule proteoglycan was determined, thus representing the first proteoglycan peptide core gene to be sequenced in its entirety [14].
• Cytotoxic cell granule-mediated apoptosis. Characterization of the macromolecular complex of granzyme B with serglycin [15].

Anatomical context of SRGN

• Serglycin-binding proteins in activated macrophages and platelets [16].
• To study the biological role of serglycin, its binding to secreted and cell-associated proteins from macrophages and blood platelets was examined [16].
• Synthesis, secretion, and subcellular localization of serglycin proteoglycan in human endothelial cells [17].
• Serglycin messenger RNA in human umbilical vein endothelial cells (HUVECs) and cultured human aortic endothelial cells was detected by reverse transcription-polymerase chain reaction [17].
• The serglycin-containing vesicles in HUVECs are distinct from the Weibel-Palade bodies, which contain von Willebrand factor [17].

Associations of SRGN with chemical compounds

• The major proteoglycan in macrophages and platelets is the chondroitin sulphate proteoglycan serglycin [16].
• Competition experiments showed that serglycin was as efficient as heparin sulfate in blocking the binding of [3H] chondrotin sulfate to PF4, whereas heparin was one order of magnitude more efficient [16].
• PRG1 was first isolated as a 200-bp cDNA clone and its progestin regulation confirmed by Northern analysis [1].
• Progestin induction of PRG1 mRNA was also inhibited by actinomycin D but not by cycloheximide [1].
• Progestin-induced increases in PRG1 mRNA were inhibited by the progestin antagonist RU 486 and occurred via the progesterone receptor [1].

Physical interactions of SRGN

• Immunoprecipitation analysis using CD44-IgG and polyclonal antibody against the serglycin core peptide demonstrated that various serglycin species capable of binding CD44 are produced by a variety of hematopoietic cells including lymphoid cells, myeloid cells, and a few tumor cell lines [18].
• We therefore propose a model where degranulated serglycin-bound granzymes require dynamin for uptake [13].
• However most importantly, serglycin-bound granzyme B in high-molecular-weight degranulate material from cytotoxic T lymphocytes predominantly followed a dynamin-dependent pathway to kill target cells [13].

Regulatory relationships of SRGN

• PRG1 is therefore a novel human gene that is directly regulated by progestins via the progesterone receptor [1].
• However, the results presented show that serglycin mRNA is expressed outside the hematopoietic cell system [19].

Other interactions of SRGN

• We previously demonstrated that chondroitin sulfate-modified serglycin is a novel ligand for CD44 involved in the adherence and activation of lymphoid cells [18].
• TNF-alpha (7 ng/ml) was the most potent inducer, increasing the level of serglycin mRNA 2.5 times after 24 h of stimulation [19].
• Confocal microscopy showed that tissue plasminogen activator was distributed similarly to serglycin [17].
• A core protein of the appropriate size for serglycin was detected by analysis of the chondroitinase-digested (35)S-sulfate-labeled HUVEC proteoglycans [17].
• With polymerase chain reaction methodology, 13 DNA probes of 250-880 base pairs in length were generated that corresponded to unique, non-Alu sequences spaced throughout the entire human serglycin gene [14].

Analytical, diagnostic and therapeutic context of SRGN

• Probes for Northern blot analysis were prepared by polymerase chain reaction (PCR) based on the sequences of human serglycin and betaglycan [20].
• N-terminal sequence and Northern blot analysis indicate that the core protein of the CSPG secreted by human macrophages is serglycin [21].
• Transmission electron microscopy revealed that the absence of serglycin did not cause any major morphological effects on peritoneal macrophages, in contrast to dramatic defects in intracellular storage vesicles in peritoneal mast cells [22].
• Immunocytochemistry revealed serglycin immunoreactivity in the Golgi area of promyelocytes (PM) and myelocytes (MC), as well as in a few band cells and mature neutrophil granulocytes [23].
• We evaluated a new portable instrument, the PPG StatPal II pH and Blood Gas Analysis System, designed for "point-of-care" measurements of blood gases and pH [24].

References